国际口腔医学杂志 ›› 2021, Vol. 48 ›› Issue (4): 450-458.doi: 10.7518/gjkq.2021065

• 综述 • 上一篇    下一篇

人乳头状瘤病毒16相关口咽鳞状细胞癌独特生物学行为及治疗的研究现状

王岳1,2(),季一鸣1,2,王晓毅3,张凌楠4,孙乐刚1,2()   

  1. 1.滨州医学院附属医院口腔颌面外科 滨州 256600
    2.滨州医学院口腔医学院 烟台 264010
    3.口腔疾病研究国家重点实验室 国家口腔疾病临床医学研究中心 四川大学华西口腔医院头颈肿瘤外科 成都 610041
    4.滨州医学院附属医院口腔正畸科 滨州 256600
  • 收稿日期:2020-11-22 修回日期:2021-03-20 出版日期:2021-07-01 发布日期:2021-06-30
  • 通讯作者: 孙乐刚
  • 作者简介:王岳,硕士,Email: 17862890372@163.com
  • 基金资助:
    山东省自然科学基金博士基金(ZR2018BH026);山东省医药卫生科技发展计划面上项目(2017WS231);滨州市社会科学规划重点研究课题(19-SKGH-31)

Unique biological behavior and treatment of the human papilloma virus 16-related oropharyngeal squamous cell carcinoma

Wang Yue1,2(),Ji Yiming1,2,Wang Xiaoyi3,Zhang Lingnan4,Sun Legang1,2()   

  1. 1. Dept. of Oral and Maxillofacial Surgery, Affiliated Hospital of Binzhou Medical University, Binzhou 256600, China
    2. School of Stomatology, Binzhou Medical University, Yantai 264010, China
    3. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
    4. Dept. of Orthodontics, Affiliated Hospital of Binzhou Medical University, Binzhou 256600, China
  • Received:2020-11-22 Revised:2021-03-20 Online:2021-07-01 Published:2021-06-30
  • Contact: Legang Sun
  • Supported by:
    Natural Science Foundation of Shandong Province(ZR2018BH026);Development Plan of Medical and Health Science and Technology in Shandong Province(2017WS231);Binzhou Social Science Planning Key Research Project(19-SKGH-31)

摘要:

人乳头状瘤病毒(HPV)感染是口咽鳞状细胞癌(OPSCC)除吸烟、饮酒外第3个独立的致病因素。其中,高危型HPV16在OPSCC发生发展中起着不可替代的重要作用,因HPV16相关OPSCC具有独特的临床病理特征,其预后及治疗方法与其他类型的OPSCC有着明显的不同。在原有治疗方法的基础上,延伸出经口腔内窥镜手术技术、放射和化学治疗、免疫治疗、疫苗预防等更为优良的治疗方法,本文主要围绕HPV16相关OPSCC独特的临床病理特征及治疗方法进行阐述。

关键词: 人乳头状瘤病毒, 口咽鳞状细胞癌, 独特临床病理特征, 治疗

Abstract:

Human papilloma virus (HPV) infection is the third-largest independent etiological factor causing orophar-yngeal squamous cell carcinoma (OPSCC) apart from smoking and drinking. High-risk HPV16 plays an important role in the occurrence and development of OPSCC. Considering its unique clinicopathologic features, the prognosis and treatment methods for HPV16-related OPSCC are significantly different from those for traditional OPSCC. Based on the original treatment methods, transoral endoscopic surgery, radiochemotherapy, immunotherapy, and vaccine treatment are extended. This paper focuses on the unique clinicopathologic features and treatment methods of HPV16-related OPSCC.

Key words: human papilloma virus, oropharyngeal squamous cell carcinoma, unique clinicopathologic features, treatment

中图分类号: 

  • R739.8

图1

HPV16的致癌机制 EGFR:表皮生长因子受体(epidermal growth factor receptor);Cyclin D1:细胞周期蛋白D1。"

表 1

HPV16不同感染状态下OPSCC的临床病理特征"

临床病理特征 HPV16相关OPSCC 传统OPSCC
发病率 增加 减少
病因 吸烟、饮酒、HPV感染 吸烟、饮酒
发病年龄 年轻化 可发于任何年龄,中老年多见
发病部位 扁桃体、舌根部 口咽部任何部位,甚至波及其他部位
症状 无明显疼痛、仅出现颈部的囊性肿大 咽喉部疼痛、吞咽异物感
淋巴结转移 早期可出现转移 任何时期均可能转移
预后 较好
[1] Machiels JP, Lambrecht M, Hanin FX, et al. Advances in the management of squamous cell carcinoma of the head and neck[J]. F1000Prime Rep, 2014,6:44.
[2] Alani RM, Münger K. Human papillomaviruses and associated malignancies[J]. J Clin Oncol, 1998,16(1):330-337.
pmid: 9440761
[3] Morshed K, Polz-Gruszka D, Szymański M, et al. Human papillomavirus (HPV)‒structure, epidemio-logy and pathogenesis[J]. Otolaryngol Pol, 2014,68(5):213-219.
doi: 10.1016/j.otpol.2014.06.001 pmid: 25283316
[4] 方三高, 魏建国, 周晓军. 解读WHO(2017)头颈部肿瘤分类: 口咽肿瘤[J]. 临床与实验病理学杂志, 2017,33(12):1301-1306.
Fang SG, Wei JG, Zhou XJ. The interpretation of oropharyngeal tumor in the classification of head and neck tumors (WHO 2017)[J]. Chin J Clin Exp Pathol, 2017,33(12):1301-1306.
[5] Candotto V, Lauritano D, Nardone M, et al. HPV infection in the oral cavity: epidemiology, clinical ma-nifestations and relationship with oral cancer[J]. Oral Implantol (Rome), 2017,10(3):209-220.
[6] Pytynia KB, Dahlstrom KR, Sturgis EM. Epidemio-logy of HPV-associated oropharyngeal cancer[J]. O-ral Oncol, 2014,50(5):380-386.
[7] Bouvard V, Baan R, Straif K, et al. A review of human carcinogens: part B: biological agents[J]. Lancet Oncol, 2009,10(4):321-322.
doi: 10.1016/S1470-2045(09)70096-8
[8] Weinberger PM, Yu Z, Haffty BG, et al. Molecular classification identifies a subset of human papillomavirus: associated oropharyngeal cancers with favorable prognosis[J]. J Clin Oncol, 2006,24(5): 736-47.
[9] Ragin CC, Taioli E. Survival of squamous cell carcinoma of the head and neck in relation to human pa-pillomavirus infection: review and meta-analysis[J]. Int J Cancer, 2007,121(8):1813-1820.
doi: 10.1002/(ISSN)1097-0215
[10] Okami K. Clinical features and treatment strategy for HPV-related oropharyngeal cancer[J]. Int J Clin Oncol, 2016,21(5):827-835.
doi: 10.1007/s10147-016-1009-6
[11] 孙云峰, 江彤, 陈传俊. 人乳头瘤病毒与口腔肿瘤及其16E5基因[J]. 国际口腔医学杂志, 2014,41(5):609-612.
Sun YF, Jiang T, Chen CJ. Relation of human papil-lomavirus and oral cancer and type 16E5 gene[J]. Int J Stomatol, 2014,41(5):609-612.
[12] Xue Y, Bellanger S, Zhang W, et al. HPV16 E2 is an immediate early marker of viral infection, preceding E7 expression in precursor structures of cervical carcinoma[J]. Cancer Res, 2010,70(13):5316-5325.
doi: 10.1158/0008-5472.CAN-09-3789
[13] Walline HM, Komarck CM McHugh JB, et al. Genomic integration of high-risk HPV alters gene expression in oropharyngeal squamous cell carcinoma[J]. Mol Cancer Res, 2016,14(10):941-952.
doi: 10.1158/1541-7786.MCR-16-0105
[14] Chung CH, Zhang Q, Kong CS, et al. p16 protein expression and human papillomavirus status as prognostic biomarkers of nonoropharyngeal head and neck squamous cell carcinoma[J]. J Clin Oncol, 2014,32(35):3930-3938.
doi: 10.1200/JCO.2013.54.5228
[15] Martinez-Zapien D, Ruiz FX, Poirson J, et al. Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53[J]. Nature, 2016,529(7587):541-545.
doi: 10.1038/nature16481 pmid: 26789255
[16] Sano D, Oridate N. The molecular mechanism of human papillomavirus-induced carcinogenesis in head and neck squamous cell carcinoma[J]. Int J Clin Oncol, 2016,21(5):819-826.
doi: 10.1007/s10147-016-1005-x
[17] Kimple RJ, Smith MA, Blitzer GC, et al. Enhanced radiation sensitivity in HPV-positive head and neck cancer[J]. Cancer Res, 2013,73(15):4791-4800.
doi: 10.1158/0008-5472.CAN-13-0587
[18] Hay A, Nixon IJ. Recent advances in the understan-ding and management of oropharyngeal cancer[J]. F1000Res, 2018,7: F1000 Faculty Rev-1362.
[19] Kreimer AR, Clifford GM, Boyle P, et al. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review[J]. Cancer Epidemiol Biomarkers Prev, 2005,14(2):467-475.
doi: 10.1158/1055-9965.EPI-04-0551
[20] Slaughter DP, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin[J]. Cancer, 1953,6(5):963-968.
doi: 10.1002/(ISSN)1097-0142
[21] Pytynia KB, Dahlstrom KR, Sturgis EM. Clinical management of squamous cell carcinoma of the oropharynx: how does this differ for HPV-related tumors[J]. Future Oncol, 2013,9(10):1413-1416.
doi: 10.2217/fon.13.121
[22] 赵艺哗, 白玉萍, 毛美玲, 等. 口咽部人乳头状瘤病毒阳性鳞状细胞癌临床病理学观察[J]. 中华病理学杂志, 2019,48(2):127-131.
Zhao YH, Bai YP, Mao ML, et al. Clinicopathological characteristics of HPV + oropharyngeal squamous cell carcinoma [J]. Chin J Pathol, 2019,48(2):127-131.
[23] Massano J, Regateiro FS, Januário G, et al. Oral squamous cell carcinoma: review of prognostic and predictive factors[J]. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2006,102(1):67-76.
pmid: 16831675
[24] Swartz JE, Pothen AJ, van Kempen PM, et al. Poor prognosis in human papillomavirus-positive oropharyngeal squamous cell carcinomas that overexpress hypoxia inducible factor-1α[J]. Head Neck, 2016,38(9):1338-1346.
doi: 10.1002/hed.v38.9
[25] Wang F, Ji X, Wang JJ, et al. LncRNA PVT1 enhances proliferation and cisplatin resistance via re-gulating miR-194-5p/HIF1a axis in oral squamous cell carcinoma[J]. Oncotargets Ther, 2020,13:243-252.
doi: 10.2147/OTT
[26] 周梁. 口咽癌诊断与治疗发展现状[J]. 中国耳鼻咽喉头颈外科, 2017,24(11):582-585.
Zhou L. Progress of the diagnosis and treatment in opharyngeal squamous cell carcinoma[J]. Chin Arch Otolaryngol Head Neck Surg, 2017,24(11):582-585.
[27] Parsons JT, Mendenhall WM, Million RR, et al. The management of primary cancers of the oropharynx: combined treatment or irradiation alone[J]. Semin Radiat Oncol, 1992,2(3):142-148.
pmid: 10717029
[28] Mydlarz WK, Chan JY, Richmon JD. The role of surgery for HPV-associated head and neck cancer[J]. Oral Oncol, 2015,51(4):305-313.
doi: 10.1016/j.oraloncology.2014.10.005
[29] Park YM, Kim HR, Cho BC, et al. Transoral robotic surgery-based therapy in patients with stage Ⅲ‒Ⅳ oropharyngeal squamous cell carcinoma[J]. Oral Oncol, 2017,75:16-21.
doi: 10.1016/j.oraloncology.2017.10.014
[30] Chao HH, Schonewolf CA, Lukens JN, et al. Outcomes for oropharyngeal squamous cell carcinoma (OPSCC) following transoral robotic surgery (TORS)[J]. Int J Radiat Oncol Biol Phys, 2018,102(3S):E234-E235.
[31] 黄冠江, 罗梦思, 张靖萱, 等. 经口机器人手术在口咽癌外科治疗中的研究进展[J]. 临床耳鼻咽喉头颈外科杂志, 2017(2):159-161.
Huang GJ, Luo MS, Zhang JX, et al. Research progress of transoral robotic surgery in oropharyn-geal cancer[J]. J Clin Otorhinolaryngol, 2017(2):159-161.
[32] Kumar B, Cipolla MJ, Old MO, et al. Surgical ma-nagement of oropharyngeal squamous cell carcinoma: survival and functional outcomes[J]. Head Neck, 2016,38(Suppl 1):E1794-E1802.
doi: 10.1002/hed.24319
[33] Gross ND, Hanna EY. The role of surgery in the management of recurrent oropharyngeal cancer[J]. Recent Results Cancer Res, 2017,206:197-205.
[34] Palma DA, Theurer J, Prisman E, et al. Radiotherapy vs. trans-oral robotic surgery for oropharyngeal squamous cell carcinoma (OPSCC): results of a randomized trial[J]. Int J Radiat Oncol Biol Phys, 2019,105(1S):S52-S53.
[35] Colevas AD, Yom SS, Pfister DG, et al. Head and neck cancers, version 1.2018 featured updates to the NCCN guidelines[J]. J Natl Compr Cancer Netw, 2018,16(5):479-490.
[36] 卢泰祥, 陈春燕. 头颈部鳞癌放射治疗现状与展望[J]. 中华肿瘤防治杂志, 2008,15(22):1681-1685.
Lu TX, Chen CY. Present and future of radiotherapy for head and neck squamous cell carcinoma[J]. Chin J Cancer Prev Treat, 2008,15(22):1681-1685.
[37] Sher DJ, Adelstein DJ, Bajaj GK, et al. Radiation therapy for oropharyngeal squamous cell carcinoma: executive summary of an ASTRO Evidence-Based Clinical Practice Guideline[J]. Pract Radiat Oncol, 2017,7(4):246-253.
doi: 10.1016/j.prro.2017.02.002
[38] Nguyen-Tan PF, Zhang Q, Ang KK, et al. Rando-mized phase Ⅲ trial to test accelerated versus standard fractionation in combination with concurrent cisplatin for head and neck carcinomas in the Radiation Therapy Oncology Group 0129 trial: long-term report of efficacy and toxicity[J]. J Clin Oncol, 2014,32(34):3858-3866.
doi: 10.1200/JCO.2014.55.3925
[39] 陆雪官, 胡超苏. 头颈部鳞癌术后辅助放化疗的研究现状[J]. 中国癌症杂志, 2017,27(6):463-470.
Lu XG, Hu CS. Adjuvant chemoradiotherapy for postoperative head and neck squamous cell carcino-ma[J]. China Oncol, 2017,27(6):463-470.
[40] 叶升, 何友谦. 复发和转移性头颈部鳞癌的化疗进展[J]. 实用癌症杂志, 2001,16(4):443-445.
Ye S, He YQ. Progression of chemotherapy in recur-rent and metastatic head and neck squamous cell car-cinoma[J]. Pract J Cancer, 2001,16(4):443-445.
[41] Kiyota N, Tahara M, Fujii M. Adjuvant treatment for post-operative head and neck squamous cell carcinoma[J]. Jpn J Clin Oncol, 2015,45(1):2-6.
doi: 10.1093/jjco/hyu195
[42] Pignon JP, le Maître A, Maillard E, et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients[J]. Radiother Oncol, 2009,92(1):4-14.
doi: 10.1016/j.radonc.2009.04.014
[43] Amini A, Karam SD. Concurrent chemotherapy in oropharyngeal cancer: cisplatin wins[J]. Oncotarget, 2019,10(6):624-625.
doi: 10.18632/oncotarget.26594 pmid: 30774757
[44] Mirghani H, Blanchard P. Treatment de-escalation for HPV-driven oropharyngeal cancer: where do we stand[J]. Clin Transl Radiat Oncol, 2018,8:4-11.
doi: 10.1016/j.ctro.2017.10.005 pmid: 29594236
[45] Sivarajah S, Kostiuk M, Lindsay C, et al. EGFR as a biomarker of smoking status and survival in oropharyngeal squamous cell carcinoma[J]. J Otolaryngol Head Neck Surg, 2019,48(1):1.
doi: 10.1186/s40463-018-0323-6
[46] House R, Majumder M, Janakiraman H, et al. Smo-king-induced control of miR-133a-3p alters the expression of EGFR and HuR in HPV-infected oropharyngeal cancer[J]. PLoS One, 2018,13(10):e0205077.
doi: 10.1371/journal.pone.0205077
[47] 王孝深, 胡超苏. 抗EGFR单抗类靶向药物在头颈部鳞癌综合治疗中的应用[J]. 中国癌症杂志, 2018,28(12):881-887.
Wang XS, Hu CS. Anti-EGFR monoclonal antibodies combined with other modalities in treatment of head and neck squamous cell carcinoma[J]. China Oncol, 2018,28(12):881-887.
[48] De Pauw I, Lardon F, Van den Bossche J, et al. Simultaneous targeting of EGFR, HER2, and HER4 by afatinib overcomes intrinsic and acquired cetuxi-mab resistance in head and neck squamous cell carcinoma cell lines[J]. Mol Oncol, 2018,12(6):830-854.
doi: 10.1002/mol2.2018.12.issue-6
[49] Sundvall M, Karrila A, Nordberg J, et al. EGFR targeting drugs in the treatment of head and neck squamous cell carcinoma[J]. Expert Opin Emerg Drugs, 2010,15(2):185-201.
doi: 10.1517/14728211003716442 pmid: 20415599
[50] Yuan C, Xu XH, Xu L, et al. Cetuximab versus nimotuzumab for the treatment of advanced nasopharyngeal carcinoma: a network meta-analysis[J]. J BUON, 2017,22(4):1004-1010.
[51] Mohamed KM, Le A, Duong H, et al. Correlation between VEGF and HIF-1alpha expression in human oral squamous cell carcinoma[J]. Exp Mol Pathol, 2004,76(2):143-152.
pmid: 15010293
[52] Ellis LM, Hicklin DJ. VEGF-targeted therapy: me-chanisms of anti-tumour activity[J]. Nat Rev Cancer, 2008,8(8):579-591.
doi: 10.1038/nrc2403
[53] Fury MG, Lee NY, Sherman E, et al. A phase 2 study of bevacizumab with cisplatin plus intensity-modulated radiation therapy for stage Ⅲ/ⅣB head and neck squamous cell cancer[J]. Cancer, 2012,118(20):5008-5014.
doi: 10.1002/cncr.27498
[54] Badoual C, Hans S, Merillon N, et al. PD-1-expres-sing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer[J]. Cancer Res, 2013,73(1):128-138.
doi: 10.1158/0008-5472.CAN-12-2606
[55] Schneider S, Kadletz L, Wiebringhaus R, et al. PD-1 and PD-L1 expression in HNSCC primary cancer and related lymph node metastasis-impact on clinical outcome[J]. Histopathology, 2018,73(4):573-584.
doi: 10.1111/his.13646 pmid: 29742291
[56] Fukushima Y, Someya M, Nakata K, et al. Influence of PD-L1 expression in immune cells on the response to radiation therapy in patients with oropharyngeal squamous cell carcinoma[J]. Radiother Oncol, 2018,129(2):409-414.
doi: S0167-8140(18)33463-7 pmid: 30249348
[57] 毛璐, 鞠侯雨, 任国欣. 程序性细胞死亡受体-1与其配体信号通路的调控及其在头颈鳞状细胞癌治疗中的研究进展[J]. 国际口腔医学杂志, 2018,45(5):560-565.
Mao L, Ju HY, Ren GX. Regulation of programmed death receptor-1 and its ligand signalling pathway and its progress in the treatment of head and neck squamous cell carcinoma[J]. Int J Stomatol, 2018,45(5):560-565.
[58] Chen G, Huang AC, Zhang W, et al. Exosomal PD-L1 contributes to immunosuppression and is asso-ciated with anti-PD-1 response[J]. Nature, 2018,560(7718):382-386.
doi: 10.1038/s41586-018-0392-8
[59] Tsakiroglou AM, Fergie M, Oguejiofor K, et al. Spatial proximity between T and PD-L1 expressing cells as a prognostic biomarker for oropharyngeal squamous cell carcinoma[J]. Br J Cancer, 2020,122(4):539-544.
doi: 10.1038/s41416-019-0634-z
[60] Kamada T, Togashi Y, Tay C, et al. PD-1 + regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer [J]. PNAS, 2019,116(20):9999-10008.
doi: 10.1073/pnas.1822001116
[61] Steuer CE, Griffith CC, Nannapaneni S, et al. A correlative analysis of PD-L1, PD-1, PD-L2, EGFR, HER2, and HER3 expression in oropharyngeal squamous cell carcinoma[J]. Mol Cancer Ther, 2018,17(3):710-716.
doi: 10.1158/1535-7163.MCT-17-0504
[62] Ribas A. Tumor immunotherapy directed at PD-1[J]. N Engl J Med, 2012,366(26):2517-2519.
doi: 10.1056/NEJMe1205943
[63] Zandberg DP, Strome SE. The role of the PD-L1:PD-1 pathway in squamous cell carcinoma of the head and neck[J]. Oral Oncol, 2014,50(7):627-632.
doi: 10.1016/j.oraloncology.2014.04.003
[64] Przybylski K, Majchrzak E, Weselik L, et al. Immunotherapy of head and neck squamous cell carcinoma (HNSCC). Immune checkpoint blockade[J]. Otolaryngol Pol, 2018,72(6):10-16.
doi: 10.5604/01.3001.0012.4367 pmid: 30647199
[65] Palmer T, Wallace L, Pollock KG, et al. Prevalence of cervical disease at age 20 after immunisation with bivalent HPV vaccine at age 12‒13 in Scotland: re-trospective population study[J]. BMJ, 2019,365:l1161.
[66] Braaten KP, Laufer MR. Human papillomavirus (HPV), HPV-related disease, and the HPV vaccine[J]. Rev Obstet Gynecol, 2008,1(1):2-10.
pmid: 18701931
[67] D’Souza G, Dempsey A. The role of HPV in head and neck cancer and review of the HPV vaccine[J]. Prev Med, 2011,53(Suppl 1):S5-S11.
doi: 10.1016/j.ypmed.2011.08.001
[68] 张婧, 陶霞. HPV疫苗研究进展及认知度、接受度现状[J]. 中国妇产科临床杂志, 2017,18(1):84-86.
Zhang J, Tao X. Progress of research recognition and acceptance of HPV vaccine[J]. Chin J Clin Obstetr Gynecol, 2017,18(1):84-86.
[69] Ahn J, Peng S, Hung CF, et al. Prophylactic immunization with human papillomavirus vaccines induces oral immunity in mice[J]. Laryngoscope, 2018,128(1):E16-E20.
doi: 10.1002/lary.v128.1
[70] Lehtinen M, Apter D, Eriksson T, et al. Effectiveness of the AS04-adjuvanted HPV-16/18 vaccine in reducing oropharyngeal HPV infections in young females‒results from a community-randomized trial[J]. Int J Cancer, 2020,147(1):170-174.
doi: 10.1002/ijc.32791 pmid: 31736068
[71] Kreimer AR, Ferreiro-Iglesias A, Nygard M, et al. Timing of HPV16-E6 antibody seroconversion before OPSCC: findings from the HPVC3 consortium[J]. Ann Oncol, 2019,30(8):1335-1343.
doi: 10.1093/annonc/mdz138
[72] Shew M, Shew ML, Bur AM. Otolaryngologists and their role in vaccination for prevention of HPV associated head & neck cancer[J]. Hum Vaccin Immunother, 2019,15(7/8):1929-1934.
doi: 10.1080/21645515.2018.1526559
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